Immunogenicity and Safety of Kinrix + (Measles Mumps Rubella) MMR Vaccine With and Without Varicella Vaccine in Healthy Children 4-6 Years

Immunogenicity and Safety Study of Kinrix® Co-administered With Varivax®

The purpose of the study is to evaluate the immunogenicity and safety of Kinrix when co-administered with varicella (Varivax® [varicella virus vaccine live], Merck and Company) and (measles mumps rubella) MMR vaccines, compared to Kinrix co-administered with MMR vaccine alone. Both Kinrix and the second dose of Varivax are indicated in children 4-6 years of age, and there is great potential for the vaccines to be given concurrently. The aim of this trial is to demonstrate that co-administered Varivax does not negatively affect the immunogenicity or reactogenicity of Kinrix.

Study Overview

• Status: Completed
• Conditions: Tetanus; Diphtheria; Acellular Pertussis
• Intervention / Treatment: Biological: GSK Biologicals'Kinrix®; Biological: Merck and Company's MMRII; Biological: Merck and Company's Varivax

Detailed Description

Subjects 4-6 years of age will be randomized into two groups to receive either Kinrix, Varivax and M-M-RII on day 0 (Group 1) or Kinrix and M-M-RII on day 0 and Varivax at month 1(Group 2).

All subjects in both groups to provide blood samples prior to vaccination on day 0 and at month 1 (for Group 2, blood sampling is prior to vaccination with Varivax).

Duration of the study will be approximately 6 months for each subject with a safety telephone contact 6 months after vaccinations.

• Study Type: Interventional
• Enrollment (Actual): 478
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Antioch, California, United States, 94509
      • GSK Investigational Site
    • Daly City, California, United States, 94015
      • GSK Investigational Site
    • Hayward, California, United States, 94545
      • GSK Investigational Site
    • Redwood City, California, United States, 94063
      • GSK Investigational Site
    • Roseville, California, United States, 95661
      • GSK Investigational Site
    • Sacramento, California, United States, 95823
      • GSK Investigational Site
    • Sacramento, California, United States, 95815
      • GSK Investigational Site
    • San Jose, California, United States, 95119
      • GSK Investigational Site
    • Santa Rosa, California, United States, 95403
      • GSK Investigational Site
    • Vallejo, California, United States, 94589
      • GSK Investigational Site
    • Walnut Creek, California, United States, 94596
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects for whom the investigator believes that their parents/ guardians can and will comply with the requirements of the protocol.
• A male or female child between 4 and 6 years of age, inclusive.
• Written informed consent obtained from the parent or guardian of the subject.
• Healthy subjects as established by medical history and clinical examination before entering into the study.
• Having received 4 doses of (Diphtheria, Tetanus Acellular Pertussis) DTaP vaccine using Pediarix and/or Infanrix, and 3 doses of poliovirus vaccine using Pediarix and/or (inactivated poliovirus vaccine, Aventis Pasteur) IPOL in the first 2 years of life.
• Previously received 1 dose of M-M-RII and Varivax (separate or combined) in the second year of life.

Exclusion Criteria:

• Use of any investigational or non-registered drug or vaccine other than the study vaccines within 30 days preceding the administration of study vaccines, or planned use during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or non-investigational product or device.
• History of previous or intercurrent diphtheria, tetanus, pertussis, polio, measles, mumps, rubella or varicella disease, or of vaccination against these diseases given after the second year of life.
• Known exposure to diphtheria, tetanus, pertussis, or polio, prior to vaccination.
• Poliovirus vaccination with one or more doses of (oral polio virus) OPV vaccine.
• Administration or planned administration of a vaccine not foreseen by the study protocol within 30 days of study vaccination and ending at Day 30.
• Chronic administration or planned administration of immunosuppressants or other immune modifying drugs within six months prior to study vaccination or planned administration during the study period ending at Day 30.
• Administration of immunoglobulins and/or any blood products at any time prior to study vaccination or planned administration during the study period ending at Day 30.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection.
• History of seizures or progressive neurological disorder, including infantile spasms, uncontrolled epilepsy or progressive encephalopathy.
• Major congenital defects or serious chronic illness.
• Acute disease at the time of enrolment.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine(s).
• History of anaphylactic reaction to egg proteins or previous doses of the vaccine(s).
• Encephalopathy within 7 days of administration of previous dose of Infanrix or Pediarix.
• Fever >=40.5°C or 104.9°F (rectal temperature) (39.5°C or 103.1°F, oral/axillary) within 48 hours of previous dose of Infanrix or Pediarix not due to another identifiable cause.
• Collapse or shock-like state within 48 hours of previous dose of DTaP or DTaP-containing vaccine.
• Persistent, severe, inconsolable screaming or crying lasting ³3 hours occurring within 48 hours of administration of previous dose of DTaP or DTaP-containing vaccine.
• Thrombocytopenia following a previous dose of M-M-RII or its component vaccines
• Inability to contact a parent/guardian of the subject by telephone.
• Blood dyscrasias, leukemia, lymphomas or other malignant neoplasms affecting the bone marrow or lymphatic systems.
• Family history of congenital or hereditary immunodeficiency, unless the immune competence of the subject has been demonstrated.
• Residence in the same household as the following persons:
• New-born infants (0-4 weeks of age).
• Pregnant mother/women without documented positive history of chickenpox disease or laboratory evidence of prior varicella vaccination.
• Pregnant women at or beyond 28 weeks gestation regardless of varicella vaccination status or varicella disease history.
• Persons with known immunodeficiency.
• Active untreated tuberculosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kinrix + M-M-R II + Varivax; Subjects received at Day 0 one dose of Kinrix, intramuscularly in the deltoid region of the left upper arm, co-administered with one dose of M-M-R II and Varivax each, subcutaneously in the deltoid of the right upper and lower arm, respectively.	Biological: GSK Biologicals'Kinrix®; One dose as intramuscular injection at visit 1; Biological: Merck and Company's MMRII; One dose as subcutaneous injection at visit 1; Biological: Merck and Company's Varivax; One dose as subcutaneous injection at visit 1 or at visit 2
Active Comparator: Kinrix + M-M-R II -> Varivax; Subjects received at Day 0 one dose of Kinrix, intramuscularly in the deltoid region of the left upper arm, co-administered with one dose of M-M-R II, subcutaneously in the deltoid of the right upper arm. At Day 30 they received one dose of Varivax subcutaneously in the deltoid region of the right upper arm.	Biological: GSK Biologicals'Kinrix®; One dose as intramuscular injection at visit 1; Biological: Merck and Company's MMRII; One dose as subcutaneous injection at visit 1; Biological: Merck and Company's Varivax; One dose as subcutaneous injection at visit 1 or at visit 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Booster Responses to Diphteria and Tetanus	Anti-diphteria (anti-D) and anti-tetanus (anti-T) booster response was defined as: initially seronegative subjects (sero-) (pre-booster antibody concentration below cut-off of < 0.1 international units per milliliter (IU/mL)) with an increase of at least four times the cut-off one month after vaccination (post-booster antibody concentration ≥0.4 IU/mL); initially seropositive subjects (sero+) (pre-booster antibody concentration ≥0.1 IU/mL) with an increase of at least four times the pre-booster antibody concentration one month after vaccination	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Number of Subjects With Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Hemagglutinin (FHA) and Anti-pertactin (Anti-PRN) Booster Responses, Measured in Enzyme-Linked Immunosorbent Assay Units Per Milliliter (EL.U/mL)	anti-PT, anti-FHA and anti-PRN booster response : initially sero- (pre-booster antibody concentration below cut-off < 5.0 EL.U/mL) with increase of at least four times cut-off one month after vaccination (concentration post-booster ≥20.0 EL.U/mL); initially sero+ with pre-booster antibody concentration ≥5.0 EL.U/mL and < 20.0 EL.U/mL with increase of at least four times pre-booster concentration one month post-booster; initially sero+ with pre-booster antibody concentration ≥20.0 EL.U/mL with an increase of at least two times the pre-booster antibody concentration one month post-booster	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Geometric Mean Titers (GMTs) for Antibodies to Poliovirus Types 1, 2 and 3	Titers are expressed as GMTs.	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Anti-D and Anti-T Antibody Concentrations Above Cut-off Value	Cut-off value was defined as greater than or equal to 1.0 international units per milliliter (IU/mL).	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Geometric Mean Concentrations (GMCs) for Anti-D and Anti-T Antibodies	Concentrations were expressed as GMCs in IU/mL.	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
GMCs for Anti-PT, Anti-FHA, Anti-PRN Antibodies	Concentrations are expressed as GMCs in Enzyme-Linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Number of Subjects With an Anti-polio 1, 2, 3 Booster Response	Anti-poliovirus 1, anti-poliovirus 2 and anti-poliovirus 3 booster response: initially seronegative subjects (pre-booster antibody titer below cut-off of 8 ED50) with an antibody titer ≥ 32 ED50 one month after vaccination; initially seropositive subjects (pre-booster antibody titers ≥ 8 ED50) with an increase at least four times the pre-booster antibody titer one month after vaccination. ED50 is defined here as the reverse of the dilution resulting in 50% inhibition. The lowest dilution at which serum samples were tested is 1:8 from which a test was considered positive.	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Number of Subjects Seroprotected Against Diphteria and Tetanus	Seroprotection status was defined as: anti-D antibody concentration greater than or equal to 0.1 IU/mL; anti-T antibody concentration greater than or equal to 0.1 IU/mL	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Number of Subjects Protected Against Poliovirus 1, 2 and 3	Seroprotection was defined: * anti-poliovirus type 1, 2 or 3 antibody titer greater than or equal to 8 ED50. ED50 is defined here as the reverse of the dilution resulting in 50% inhibition.	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Number of Subjects Seropositive for Anti-PT, Anti-FHA and Anti-PRN Antibodies	Seropositivity was defined as a concentration greater than or equal to 5.0 EL.U/mL	One month after Kinrix vaccination (Month 1), prior to Varivax vaccination for Kinrix + M-M-R II -> Varivax Group.
Number of Subjects With Any Solicited Local Symptoms	Solicited local symptoms included pain, redness and swelling at the injection site. Any was defined as incidence of a particular symptom regardless of intensity grade.	Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
Number of Subjects With Any Solicited General Symptoms	Solicited general symptoms included fever [temperature equal to or greater than 37.5 degrees Celsius (°C)], drowsiness and loss of appetite. Any was defined as incidence of a particular symptom regardless of intensity grade.	Within 4 days (Day 0 to 3) after booster immunization * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
Number of Subjects With Unsolicited Adverse Events	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study. Also any "solicited" symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.	Up to 31 days (Day 0 through Day 30) after booster vaccination * for Kinrix + M-M-R II -> Varivax Group before vaccination with Varivax
Number of Subjects With Serious Adverse Events (SAEs)	Serious adverse events are medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.	During the entire study period (from Day 0 to 6 months post-vaccination)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Klein NP, Weston WM, Kuriyakose S, Kolhe D, Howe B, Friedland LR, Van Der Meeren O. An open-label, randomized, multi-center study of the immunogenicity and safety of DTaP-IPV (Kinrix) co-administered with MMR vaccine with or without varicella vaccine in healthy pre-school age children. Vaccine. 2012 Jan 11;30(3):668-74. doi: 10.1016/j.vaccine.2011.10.065. Epub 2011 Nov 4.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: March 31, 2009
• Primary Completion (Actual): January 15, 2010
• Study Completion (Actual): June 15, 2010

Study Registration Dates

• First Submitted: March 26, 2009
• First Submitted That Met QC Criteria: March 26, 2009
• First Posted (Estimate): March 30, 2009

Study Record Updates

• Last Update Posted (Actual): August 22, 2018
• Last Update Submitted That Met QC Criteria: July 25, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Booster; Immunization; Preschool; Co-administration
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Corynebacterium Infections; Diphtheria
• Other Study ID Numbers: 111852

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 111852
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 111852
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 111852
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 111852
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Study Protocol
   Information identifier: 111852
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 111852
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 111852
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register